BACKGROUND:During bone remodeling,bone formation and bone resorption are spatially and temporally coordinated,involving intricate interactions between osteoclasts and osteoblasts.Isoginkgetin,a flavonoid found in Ginkgo biloba,has a wide range of anticancer activity and anti-reactive oxygen species activity;however,the effect of isoginkgetin on osteoclast differentiation is unknown.OBJECTIVE:To study the effect and mechanism of action of isoginkgetin on osteoclastogenesis.METHODS:In vitro studies were performed on mouse bone marrow-derived macrophages,and cell counting kit-8 cytotoxicity assay was used to detect the effect of isoginkgetin on cell viability of bone marrow-derived macrophages.Macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand were used to induce the differentiation of bone marrow-derived macrophages to osteoclasts.Network pharmacology and molecular docking and molecular dynamics simulations were used to predict the processes and targets of the effects of isoginkgetin on the differentiation of osteoclasts.Tartrate-resistant acid phosphatase staining and F-actin staining were used to detect the effects of isoginkgetin on the differentiation and function of osteoclasts.Western blot and RT-PCR were used to detect the effects of isoginkgetin on the expression of genes and proteins related to osteoclast differentiation,reactive oxygen species,and PI3K/AKT pathways.Fluorescent probes were used to detect cellular and mitochondrial reactive oxygen species levels.Flow cytometry technology was used to detect reactive oxygen species levels in cells.RESULTS AND CONCLUSION:(1)Network pharmacology results showed that isoginkgetin affected osteoporosis mainly through the PI3K-AKT pathway and cellular response to drugs and hypoxia,and GSK3β,ESR1,MCL1 and CCNA2 were the key targets.(2)Cell counting kit-8 and tartrate-resistant acid phosphatase staining results showed that isoginkgetin at 8 μmol/L had the most significant inhibitory effect on osteoclastogenesis in vitro,and F-actin results showed that isoginkgetin inhibited osteoclast cytoskeletal actin ring formation in a concentration-dependent manner.(3)Molecular dynamics simulations showed that isoginkgetin bound well to osteoclastogenesis marker proteins(NFATc1,c-Fos,CTSK,and MMP9).Western blot and RT-PCR results indicated that isoginkgetin inhibited the expression of osteoclastogenesis marker proteins and genes(NFATc1,c-Fos,CTSK,and MMP9).(4)Western blot results showed that isoginkgetin inhibited the phosphorylation level of PI3K/AKT/GSK3β and suppressed osteoclastogenesis by activating the PI3K-AKT-GSK3β pathway.(5)The results of reactive oxygen species assay showed that isoginkgetin significantly reduced receptor activator of nuclear factor kappa-B ligand-induced cellular and mitochondrial reactive oxygen species production,and inhibited the differentiation of bone marrow-derived macrophages to osteoclasts.

BACKGROUND:During bone remodeling,bone formation and bone resorption are spatially and temporally coordinated,involving intricate interactions between osteoclasts and osteoblasts.Isoginkgetin,a flavonoid found in Ginkgo biloba,has a wide range of anticancer activity and anti-reactive oxygen species activity;however,the effect of isoginkgetin on osteoclast differentiation is unknown.OBJECTIVE:To study the effect and mechanism of action of isoginkgetin on osteoclastogenesis.METHODS:In vitro studies were performed on mouse bone marrow-derived macrophages,and cell counting kit-8 cytotoxicity assay was used to detect the effect of isoginkgetin on cell viability of bone marrow-derived macrophages.Macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand were used to induce the differentiation of bone marrow-derived macrophages to osteoclasts.Network pharmacology and molecular docking and molecular dynamics simulations were used to predict the processes and targets of the effects of isoginkgetin on the differentiation of osteoclasts.Tartrate-resistant acid phosphatase staining and F-actin staining were used to detect the effects of isoginkgetin on the differentiation and function of osteoclasts.Western blot and RT-PCR were used to detect the effects of isoginkgetin on the expression of genes and proteins related to osteoclast differentiation,reactive oxygen species,and PI3K/AKT pathways.Fluorescent probes were used to detect cellular and mitochondrial reactive oxygen species levels.Flow cytometry technology was used to detect reactive oxygen species levels in cells.RESULTS AND CONCLUSION:(1)Network pharmacology results showed that isoginkgetin affected osteoporosis mainly through the PI3K-AKT pathway and cellular response to drugs and hypoxia,and GSK3β,ESR1,MCL1 and CCNA2 were the key targets.(2)Cell counting kit-8 and tartrate-resistant acid phosphatase staining results showed that isoginkgetin at 8 μmol/L had the most significant inhibitory effect on osteoclastogenesis in vitro,and F-actin results showed that isoginkgetin inhibited osteoclast cytoskeletal actin ring formation in a concentration-dependent manner.(3)Molecular dynamics simulations showed that isoginkgetin bound well to osteoclastogenesis marker proteins(NFATc1,c-Fos,CTSK,and MMP9).Western blot and RT-PCR results indicated that isoginkgetin inhibited the expression of osteoclastogenesis marker proteins and genes(NFATc1,c-Fos,CTSK,and MMP9).(4)Western blot results showed that isoginkgetin inhibited the phosphorylation level of PI3K/AKT/GSK3β and suppressed osteoclastogenesis by activating the PI3K-AKT-GSK3β pathway.(5)The results of reactive oxygen species assay showed that isoginkgetin significantly reduced receptor activator of nuclear factor kappa-B ligand-induced cellular and mitochondrial reactive oxygen species production,and inhibited the differentiation of bone marrow-derived macrophages to osteoclasts.

Objective:To explore the differences of cortical responses to unilateral upper limb training (UULT) in subacute stroke patients with different motor-evoked potentials (MEPs).Methods:A cross-sectional study was performed; 33 subacute stroke patients accepted UULT were recruited from Center of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University from August 2023 to August 2024. Transcranial magnetic stimulation was used to assess MEPs, and functional near-infrared spectroscopy (fNIRS) was used to record hemodynamic changes in bilateral primary motor cortex (M1), pre-motor cortex/supplementary motor area (PMC/SMA), and posterior parietal cortex (PPC) during the resting state and UULT task state. Wavelet coherence analysis and Granger causality analysis were used to determine the strengths of functional connectivity (FC) and effective connectivity (EC) between brain regions.Results:Among the 33 patients, 16 were assigned to an absent MEP (MEP -) group and 17 into a present MEP (MEP +) group (MEP amplitude: [310±200] μV). In the MEP - group, compared with those during the resting state, FC of ipsilesional M1 with contralesional PPC, contralesional M1, ipsilesional PPC, contralesional PMC/SMA and ipsilesional PMC/SMA during the task state (0.64±0.14 vs. 0.48±0.12, 0.63±0.14 vs. 0.45±0.10, 0.70±0.14 vs. 0.56±0.12, 0.56±0.13 vs. 0.39±0.15, 0.61±0.13 vs. 0.44±0.14), and FC between the ipsilesional PMC/SMA and ipsilesional PPC during the task state (0.71±0.12 vs. 0.61±0.09) were significantly decreased ( P<0.0033); compared with that during the resting state, EC from the ipsilesional PPC to the ipsilesional PMC/SMA during the task state (0.15±0.07 vs. 0.25±0.18) was significantly increased ( P<0.05). In the MEP + group, compared with that during the resting state, FC of the ipsilesional M1 with contralesional M1 and ipsilesional PPC during the task state (0.81±0.08 vs. 0.70±0.14, 0.78±0.08 vs. 0.68±0.13) was significantly decreased ( P<0.0033); compared with that during the resting state, EC from contralesional M1 to ipsilesional M1 during the task state (0.11±0.10 vs. 0.15±0.10) was significantly increased ( P<0.05). No significant differences were noted in changes of FC strength between resting state and UULT task state across brain regions when comparing the MEP - and MEP + groups ( P>0.0033). Conclusion:MEP - subacute stroke patients exhibit extensive bilateral cortical response during the UULT task state, whereas MEP + patients show limited cortical response, which indicate that rehabilitation training strategy in MEP + patients needs to be adjusted.

Fe/Mn/Gd polymetallic nanooxide(FMGN)were prepared by one-step solvent thermal reaction by using Fe(acac)3,Mn(acac)2 and Gd(acac)3 as reaction precursors.Next,hyaluronic acid(HA)was used to modify FMGN to fabricate tumor-targeting T 1-T 2 dual-mode magnetic resonance imaging(MRI)contrast agent(HA-FMGN)for accurate diagnosis of prostate cancer.The structure and morphology of FMGN were observed by transmission electron microscope(TEM).It was found that FMGN exhibited a uniform nanocluster spherical structure when the feeding ratio of iron acetylacetonate,manganese acetylacetonate,and gadolinium acetylacetonate was 3:2:1.X-ray diffraction(XRD)analysis showed that FMGN had a typical inverse spinel structure of Mn doped Fe 3O 4,with Gd existing in the form of amorphous gadolinium oxide.The longitudinal relaxivity(r 1)and transverse relaxivity(r 2)of FMGN were 13.395 and 428.535 L/(mmol·s),respectively,measured by 0.5 T MRI analyzer,which proved that FMGN had excellent T 1-T 2 dual-mode MRI contrast capability.The cytotoxicity and hemolysis test found that HA-FMGN didn't damage red cells and induce toxicity for normal cells,indicating that HA-FMGN had excellent cell biocompatibility.The internalization efficacy of HA-FMGN was observed by CLSM,and the results showed that HA-FMGN possessed excellent prostate tumor-targeting ability.In vivo MRI experiment showed that HA-FMGN significantly enhanced T 1 and T 2 weighted MRI signal to noise ratio(SNR)of prostate tumor,which promoted the accurate diagnosis of orthotopic prostate cancer.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Hospital culture is the sum of common values， codes of conduct， and working methods formed by internal employees within the hospital， and it is the spiritual pillar and core of cohesion of the hospital. Party-building leadership plays an important role in promoting hospital culture construction， including strengthening values guidance， enhancing team cohesion， facilitating management system innovation， and shaping social image and brand value. By analyzing the effectiveness of a series of Party-building activities carried out by Xi’an No. 9 Hospital in recent years， this paper explored the effect and significance of Party-building leadership in promoting hospital culture construction in the new era， as well as proposed guiding strategies for strengthening Party-building work in promoting hospital culture construction in the new era， so as to promote high-quality development of the hospital.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To explore the differences of cortical responses to unilateral upper limb training (UULT) in subacute stroke patients with different motor-evoked potentials (MEPs).Methods:A cross-sectional study was performed; 33 subacute stroke patients accepted UULT were recruited from Center of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University from August 2023 to August 2024. Transcranial magnetic stimulation was used to assess MEPs, and functional near-infrared spectroscopy (fNIRS) was used to record hemodynamic changes in bilateral primary motor cortex (M1), pre-motor cortex/supplementary motor area (PMC/SMA), and posterior parietal cortex (PPC) during the resting state and UULT task state. Wavelet coherence analysis and Granger causality analysis were used to determine the strengths of functional connectivity (FC) and effective connectivity (EC) between brain regions.Results:Among the 33 patients, 16 were assigned to an absent MEP (MEP -) group and 17 into a present MEP (MEP +) group (MEP amplitude: [310±200] μV). In the MEP - group, compared with those during the resting state, FC of ipsilesional M1 with contralesional PPC, contralesional M1, ipsilesional PPC, contralesional PMC/SMA and ipsilesional PMC/SMA during the task state (0.64±0.14 vs. 0.48±0.12, 0.63±0.14 vs. 0.45±0.10, 0.70±0.14 vs. 0.56±0.12, 0.56±0.13 vs. 0.39±0.15, 0.61±0.13 vs. 0.44±0.14), and FC between the ipsilesional PMC/SMA and ipsilesional PPC during the task state (0.71±0.12 vs. 0.61±0.09) were significantly decreased ( P<0.0033); compared with that during the resting state, EC from the ipsilesional PPC to the ipsilesional PMC/SMA during the task state (0.15±0.07 vs. 0.25±0.18) was significantly increased ( P<0.05). In the MEP + group, compared with that during the resting state, FC of the ipsilesional M1 with contralesional M1 and ipsilesional PPC during the task state (0.81±0.08 vs. 0.70±0.14, 0.78±0.08 vs. 0.68±0.13) was significantly decreased ( P<0.0033); compared with that during the resting state, EC from contralesional M1 to ipsilesional M1 during the task state (0.11±0.10 vs. 0.15±0.10) was significantly increased ( P<0.05). No significant differences were noted in changes of FC strength between resting state and UULT task state across brain regions when comparing the MEP - and MEP + groups ( P>0.0033). Conclusion:MEP - subacute stroke patients exhibit extensive bilateral cortical response during the UULT task state, whereas MEP + patients show limited cortical response, which indicate that rehabilitation training strategy in MEP + patients needs to be adjusted.

The purpose of this study was to enrich the genomic information and provide a basis for further development and utilization of Polygonatum kingianum. The fresh rhizome of P. kingianum was used as the experimental material, and the full-length transcriptome was sequenced by PacBio Sequel platform. The final measured polymerase reads were 1 120 485, with a total of 77.73 GB of data. In NR database, 41 864 homologous sequence alignments were aligned to 5 species; 40 506 were annotated in the KOG database and classified into 26 categories based on their functionality; 69 060 GO annotated 32 functional groups divided into 3 categories: cellular components, molecular functions, and biological processes; 45 779 annotations were added to 145 metabolic pathways in the KEGG database. Among them, there are 127 identified transcripts related to polysaccharide synthesis in the glycolysis/gluconeogenesis metabolic pathway, 144 in the starch and sucrose metabolic pathway, 85 in the amino acid sugar and nucleotide sugar metabolic pathway, and 69 in the fructose and mannose metabolic pathway. In addition, 1 781 transcription factors were detected, distributed in 37 transcription factor families; 180 293 SSR loci were detected, among which single base repeats accounted for the most, accounting for 30.48% of all base repeats, and at least five base repeats, accounting for only 0.14% of single base repeats. The results of this study provide important data supporting for enriching the genomic information of P. kingianum and exploring its effective biosynthetic pathway.